Yuning Zhang, Xiaolei Sun, Yawei Jin, Kanghui Chen, Lu Zhang, Xiong Gao, Mohan Li, Ze Yuan, Jianguo Jia, Aijun Sun, Junbo Ge
{"title":"线粒体移植增强心肌损伤后巨噬细胞的修复能力。","authors":"Yuning Zhang, Xiaolei Sun, Yawei Jin, Kanghui Chen, Lu Zhang, Xiong Gao, Mohan Li, Ze Yuan, Jianguo Jia, Aijun Sun, Junbo Ge","doi":"10.1002/advs.202506337","DOIUrl":null,"url":null,"abstract":"<p><p>The pathologically remodeled myocardial ischemic microenvironment, characterized by sustained hypoxia, metabolic insufficiency, and accumulation of inflammatory mediators, severely disrupts mitochondrial homeostasis. This dysfunction establishes a self-perpetuating cycle that impairs the coordinated healing cascade and compromises cardiac tissue repair following myocardial infarction (MI). To counteract these effects, a novel strategy of mitochondrial augmentation is proposed, whereby healthy exogenous mitochondria are introduced into macrophages to generate mitochondria-transplanted macrophages (Mito-T-Macros or MTMs), which can resist post-MI stress. Mitochondrial transplantation (MT) effectively induces macrophage polarization toward a reparative M2-like phenotype, thereby enhancing pro-healing functions, including migration, invasion, and phagocytosis. In vivo, MTM therapy enhances cardiac function after MI and attenuates left ventricular remodeling by reducing fibrosis, limiting apoptosis, and promoting angiogenesis. Mechanistically, MT accelerates the phenotypic transition of macrophages to a reparative state and prolongs their activity during the healing phase. Notably, a portion of the transplanted mitochondria are released from MTMs and subsequently internalized by cardiomyocytes, suggesting an additional mechanism of myocardial support. Overall, MT enhances the reparative capabilities of macrophages and contributes to the therapeutic efficacy of MTMs in ameliorating post-MI cardiac remodeling. These findings support MTM therapy as a promising and innovative approach for repairing myocardial injury following MI.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e06337"},"PeriodicalIF":14.1000,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mitochondrial Transplantation Augments the Reparative Capacity of Macrophages Following Myocardial Injury.\",\"authors\":\"Yuning Zhang, Xiaolei Sun, Yawei Jin, Kanghui Chen, Lu Zhang, Xiong Gao, Mohan Li, Ze Yuan, Jianguo Jia, Aijun Sun, Junbo Ge\",\"doi\":\"10.1002/advs.202506337\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The pathologically remodeled myocardial ischemic microenvironment, characterized by sustained hypoxia, metabolic insufficiency, and accumulation of inflammatory mediators, severely disrupts mitochondrial homeostasis. This dysfunction establishes a self-perpetuating cycle that impairs the coordinated healing cascade and compromises cardiac tissue repair following myocardial infarction (MI). To counteract these effects, a novel strategy of mitochondrial augmentation is proposed, whereby healthy exogenous mitochondria are introduced into macrophages to generate mitochondria-transplanted macrophages (Mito-T-Macros or MTMs), which can resist post-MI stress. Mitochondrial transplantation (MT) effectively induces macrophage polarization toward a reparative M2-like phenotype, thereby enhancing pro-healing functions, including migration, invasion, and phagocytosis. In vivo, MTM therapy enhances cardiac function after MI and attenuates left ventricular remodeling by reducing fibrosis, limiting apoptosis, and promoting angiogenesis. Mechanistically, MT accelerates the phenotypic transition of macrophages to a reparative state and prolongs their activity during the healing phase. Notably, a portion of the transplanted mitochondria are released from MTMs and subsequently internalized by cardiomyocytes, suggesting an additional mechanism of myocardial support. Overall, MT enhances the reparative capabilities of macrophages and contributes to the therapeutic efficacy of MTMs in ameliorating post-MI cardiac remodeling. These findings support MTM therapy as a promising and innovative approach for repairing myocardial injury following MI.</p>\",\"PeriodicalId\":117,\"journal\":{\"name\":\"Advanced Science\",\"volume\":\" \",\"pages\":\"e06337\"},\"PeriodicalIF\":14.1000,\"publicationDate\":\"2025-08-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced Science\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://doi.org/10.1002/advs.202506337\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Science","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1002/advs.202506337","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Mitochondrial Transplantation Augments the Reparative Capacity of Macrophages Following Myocardial Injury.
The pathologically remodeled myocardial ischemic microenvironment, characterized by sustained hypoxia, metabolic insufficiency, and accumulation of inflammatory mediators, severely disrupts mitochondrial homeostasis. This dysfunction establishes a self-perpetuating cycle that impairs the coordinated healing cascade and compromises cardiac tissue repair following myocardial infarction (MI). To counteract these effects, a novel strategy of mitochondrial augmentation is proposed, whereby healthy exogenous mitochondria are introduced into macrophages to generate mitochondria-transplanted macrophages (Mito-T-Macros or MTMs), which can resist post-MI stress. Mitochondrial transplantation (MT) effectively induces macrophage polarization toward a reparative M2-like phenotype, thereby enhancing pro-healing functions, including migration, invasion, and phagocytosis. In vivo, MTM therapy enhances cardiac function after MI and attenuates left ventricular remodeling by reducing fibrosis, limiting apoptosis, and promoting angiogenesis. Mechanistically, MT accelerates the phenotypic transition of macrophages to a reparative state and prolongs their activity during the healing phase. Notably, a portion of the transplanted mitochondria are released from MTMs and subsequently internalized by cardiomyocytes, suggesting an additional mechanism of myocardial support. Overall, MT enhances the reparative capabilities of macrophages and contributes to the therapeutic efficacy of MTMs in ameliorating post-MI cardiac remodeling. These findings support MTM therapy as a promising and innovative approach for repairing myocardial injury following MI.
期刊介绍:
Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.